Inflammation Research

, Volume 62, Issue 1, pp 89–96 | Cite as

Lipopolysaccharide/adenosine triphosphate-mediated signal transduction in the regulation of NLRP3 protein expression and caspase-1-mediated interleukin-1β secretion

  • Pei-Chun Liao
  • Louis Kuoping Chao
  • Ju-Ching Chou
  • Wei-Chih Dong
  • Chien-Nan Lin
  • Chai-Yi Lin
  • Ann Chen
  • Shuk-Man Ka
  • Chen-Lung Ho
  • Kuo-Feng Hua
Original Research Paper



Reactive oxygen species (ROS) plays a critical role in the regulation of NLRP3 inflammasome activation. However, the ROS-mediated signaling pathways controlling NLRP3 inflammasome activation are not well defined.


Using lipopolysaccharide (LPS) and adenosine triphosphate (ATP) activated murine macrophages as the testing model, cytokine release and protein expression were quantified by enzyme-linked immunosorbent assay and Western blot, respectively. ROS was scavenged by N-acetyl cysteine; NADPH oxidase, the major source of ROS, was inhibited by diphenyliodonium, apocynin or gp91-phox siRNA transfection; and protein kinase was inhibited by its specific inhibitor.


LPS-induced NLRP3 protein expression was regulated through the NADPH oxidase/ROS/NF-κB-dependent, JAK2/PI3-kinase/AKT/NF-κB-dependent, and MAPK-dependent pathways, while ATP-induced caspase-1 activation was regulated through the NADPH oxidase/ROS-dependent pathway.


These results demonstrate that ROS regulates not only the priming stage, but also the activation stage, of NLRP3 inflammasome activation in LPS + ATP-activated macrophages.


NLRP3 inflammasome LPS Reactive oxygen species 



This work was supported by the National Science Council, Taiwan: contract grant numbers: NSC 98-2320-B-039-003-MY2 (KF Hua); 100-2313-B-197-002 (KF Hua).


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Copyright information

© Springer Basel AG 2012

Authors and Affiliations

  • Pei-Chun Liao
    • 1
    • 2
  • Louis Kuoping Chao
    • 2
  • Ju-Ching Chou
    • 1
  • Wei-Chih Dong
    • 1
  • Chien-Nan Lin
    • 1
  • Chai-Yi Lin
    • 1
  • Ann Chen
    • 4
  • Shuk-Man Ka
    • 5
  • Chen-Lung Ho
    • 3
  • Kuo-Feng Hua
    • 1
  1. 1.Department of Biotechnology and Animal ScienceNational Ilan UniversityIlanTaiwan
  2. 2.Department of CosmeceuticsChina Medical UniversityTaichungTaiwan
  3. 3.Division of Wood CelluloseTaiwan Forestry Research InstituteTaipeiTaiwan
  4. 4.Department of Pathology, Tri-Service General HospitalNational Defense Medical CenterTaipeiTaiwan
  5. 5.Graduate Institute of Aerospace and Undersea MedicineNational Defense Medical CenterTaipeiTaiwan

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